Assist devices fail to reverse patterns of fetal gene expression despite β-blockers
Assist devices fail to reverse patterns of fetal gene expression despite β-blockers
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DOI：
10.1016/j.healun.2007.08.003
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发表时间：
2007-11-01
影响因子：
8.9
通讯作者：
Cleveland, Joseph, Jr.
中科院分区：
文献类型：
--
作者：
Lowes, Brian D.;Zolty, Ronald;Cleveland, Joseph, Jr.
背景：心力衰竭与收缩和代谢基因的胎儿基因表达模式逆转有关。使用辅助装置后心室功能的实质性恢复是罕见的。我们的目标是评估胎儿基因表达和缺氧诱导因子-1 α（HIF-1 α），缺氧signaling.Methods转录因子的辅助装置的影响：人类心脏组织获得从左心室心尖在辅助装置植入的时间，并再次从左心室游离壁在心脏移植。非衰竭组织从来自人类供体的未使用的心脏获得。用Affyellow 133 plus 2阵列测量基因表达。HIF-1 α通过Western blotting与市售antibodies.Results：心力衰竭与α-肌球蛋白重链和肌浆网-Ca 2+腺苷三磷酸酶信使RNA表达的减少沿着骨骼肌原肌球蛋白的增加有关。这种模式在辅助器械治疗后持续存在。心力衰竭还与包括葡萄糖转运蛋白1（GLUT 1）在内的调节代谢基因的异常有关。这些模式也坚持辅助装置治疗后，尽管减少心房利钠肽的表达和正常化的HIF-1 alpha.Conclusions：辅助装置产生持续恢复心肌收缩功能的失败可能部分是由于持续的胎儿收缩和代谢基因的转录模式。J Heart Lung Transplant 2007; 26：1170 - 6.版权所有（c）2007国际心肺移植学会。
Background: Heart failure is associated with reversal to a fetal gene expression pattern of contractile and metabolic genes. Substantial recovery of ventricular function with assist devices is rare. Our goal was to evaluate the effects of assist devices on fetal gene expression and hypoxia inducible factor-1 alpha (HIF-1 alpha), a transcriptional factor in hypoxic signaling.Methods: Human heart tissue was obtained from the left ventricular apex at the time of assist device implantation and again from the left ventricular free wall during cardiac transplantation. Non-failing tissue was obtained from unused hearts from human donors. Gene expression was measured with the Affymetrix 133 plus 2 Array. HIF-1 alpha was measured by Western blotting with commercially available antibodies.Results: Heart failure was associated with a decrease in alpha-myosin heavy chain and sarcoplasmic reticulum-Ca2+ adenosine triphosphatase messenger RNA expression along with an increase in skeletal tropomyosin. This pattern persisted after assist device therapy. Heart failure was also associated with abnormalities in regulatory metabolic genes including glucose transporter 1 (GLUT1). These patterns also persisted after assist device therapy despite a reduction in atrial natriuretic peptide expression and normalization of HIF-1 alpha.Conclusions: Failure of assist devices to produce sustained recovery of myocardial contractile function may be due in part to persistent fetal transcriptional patterns of contractile and metabolic genes. J Heart Lung Transplant 2007; 26:1170 - 6. Copyright (c) 2007 by the International Society for Heart and Lung Transplantation.